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In vitro: ASC-J9 is able to degrade fAR and AR3 in a dose-dependent manner in various human PCa cells. ASC-J9 can also effectively suppress AR-targeted genes in CWR22Rv1-fARKD cells. ASC-J9 (5 or 10 µM) significantly suppresses the DHT-induced cell growth in all three PCa cell lines. ASC-J9 suppresses AR-targeted genes and cell growth by degradation of fAR and ectopic AR3 in C81 and C4-2 cells. ASC-J9 selectively promotes AR degradation by disrupting the interaction between AR and AR coregulators. ASC-J9 reduces the AR aggregated AR-112Q in cells.
In vivo: ASC-J9 (75 mg/kg, i.p.) degrades both fAR and AR3 in the xenografted tumors in vivo, and SC-J9-treated tumors has significantly decreased Ki67-positive cells. ASC-J9 (50 mg/kg every 48 h, i.p.) substantially ameliorates the SBMA symptoms in AR-97Q mice, and ameliorates neuromuscular pathological findings. The ASC-J9-treated SBMA mice have relatively normal serum testosterone concentrations. ASC-J9-treated mice show significantly smaller prostate tumor sizes when compared with those receiving classic ADT/castration with little serum androgen.
| Cell Experiment | |
|---|---|
| Cell lines | PC12/AR-112Q and PC12/AR-10Q cells |
| Preparation method | For the cell survival assay, the PC12/AR-112Q and PC12/AR-10Q cells are cultured as described previously and incubated cells in the presence of 10 μg/mL doxycycline for 24 h. Then the cells are treated with vehicle, 5 μM ASC-J9 or 10 μM ASC-J9, along with 1 nM DHT, and determined cell viability using Trypan blue staining at specific time intervals. |
| Concentrations | |
| Incubation time | |
| Animal Experiment | |
|---|---|
| Animal models | both anterior prostates of castrated nude mouse |
| Formulation | |
| Dosages | 75 mg/kg |
| Administration | intraperitoneal injection |
| Molecular Weight | 396.43 |
| Formula | C23H24O6 |
| CAS Number | 52328-98-0 |
| Solubility (25°C) | DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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